The goal of this project is to localize the neural substrates of target-directed reaching in humans. Functional brain mapping with 15-O positron emission tomography (PET) will be used to image task-related changes in regional cerebral blood flow (rCBF) in normal human volunteers, and transcranial magnetic stimulation (TMS) will be used to reversibly disrupt the functioning of selected cortical areas of subjects performing a variety of targeted reaching tasks. While the substrates of motor learning have been mapped in some detail, much less is known about the substrates of on-line error correction, long-term sensorimotor adaptation, and coordination of visual and kinesthetic control signals. There are three specific aims, corresponding to the issues: Specific Aim 1: To delineate the respective neural substrates for visual versus kinesthetic control of targeted reaching. Three experiments will address this aim, each with a separate group of subjects (10 subjects per experiment), using targeted reaching paradigms that dissociate visual and kinesthetic targeting and trajectory control. Exp. 1.1: PET study of visual versus kinesthetic targeting and guidance of reaching. Exp. 1.2: PET study of visual versus kinesthetic guidance during on-line error correction. Exp. 1.3: PET study of visual versus kinesthetic trajectory guidance during prism adaptation. Specific Aim 2: To identify the neural substrates for on-line error correction and motor error-induced sensorimotor adaptation in targeted reaching. Four experiments are planned and each will involve set of targeted reaching paradigms to dissociate on-line error correction and motor error-induced sensorimotor adaptation. Exp. 2.1: PET study of on-line error correction versus motor error-induced sensorimotor adaptation. Exp. 2.2: PET study of limb versus oculomotor components of motor error-induced sensorimotor adaptation. Exp. 2.3: PET study of conscious versus subliminal on-line error correction. Exp. 2.4: TMS study of posterior parietal contribution to on-line error correction: overt versus subliminal target displacements and visual versus kinesthetic guidance of reaching trajectory. Specific Aim 3: To identify the neural substrates for sensorimotor adaptation induced by perceptual distortions (sensory mismatch and reafference mismatch) during target-directed reaching. Four experiments are planned. Each will involve a set of targeted reaching paradigms that dissociate the three factors implicated in long-term sensorimotor adaptation: sensory mismatch, reafferance mismatch, and motor error. Exp. 3.1: PET study of active versus passive prism adaptation. Exp. 3.2: PET study of prism adaptation with and without visual motor error. Exp. 3.3: PET study of cognitive factors in prism adaptation. Exp. 3.4: TMS study of lateral prefrontal versus posterior parietal effects on prism adaptation.